Clinical and histological predictive factors of reclassification of prostate cancer patients on active surveillance.

INTRODUCTION AND OBJECTIVE: Active surveillance (AS) has been established as a therapeutic strategy in patients with low-risk prostate cancer. Demographic and anatomopathological factors that increase the probability of reclassifying patients have been identified. MATERIALS AND METHODS: Laboratory and histopathological data were collected from 116 patients included on AS since 2014. Univariate analysis was performed with Chi-square, t-student and Kendall's Tau, multivariate analysis according to logistic regression and Kaplan-Meier curves were calculated. RESULTS: Of the 116 patients in AS, the median age at diagnosis was 66 years and the median follow-up was 13 months (2-72). Of these, 61 (52.6%) are still on surveillance, while 55 (47.4%) have left the program, mostly due to histological progression (52 patients (45.2%)); radical prostatectomy was performed in 27 (49.1%). Prostate volume (PV)≤60cc and the number of positive cylinders >1 in diagnostic biopsy (P=.05) were associated with higher reclassification rate in univariate analysis (P<.05). Multivariate analysis showed that these two variables significantly correlated with higher reclassification rate (PV 60 cc: OR 4.39, P=.04; >1 positive cylinder at diagnostic biopsy: OR 2.48, P=.03). CONCLUSIONS: It has been shown that initial ultrasound volume and the number of positive cylinders in the diagnostic biopsy are independent risk factors for reclassification. Initial PSA, laterality of the affected cylinders and PSA density were not predictive factors of progression in our series.

Factores clínicos e histológicos predictores de reclasificación en pacientes incluidos en programa de vigilancia activa de cáncer de próstata / Clinical and histological predictive factors of reclassification of prostate cancer patients on active surveillance

Introducción y objetivo La vigilancia activa (VA) se ha establecido como estrategia terapéutica en pacientes con cáncer de próstata de bajo riesgo. Se han identificado factores demográficos y anatomopatológicos que aumentan la probabilidad de reclasificar a los enfermos. Materiales y métodos Se han recogido datos analíticos e histopatológicos de 116 pacientes incluidos en VA desde 2014. Se ha realizado un análisis univariante con X2, t de Student y Tau de Kendall, un análisis multivariante según regresión logística y se han calculado las curvas de Kaplan-Meier. Resultados De los 116 pacientes en VA, la mediana de edad al diagnóstico fue 66 años y la mediana de seguimiento fueron 13 meses (2-72). De todos ellos, 61 (52,6%) siguen en vigilancia mientras que 55 (47,4%) han salido del programa, la mayoría por progresión histológica (52 pacientes [45,2%]), realizándose prostatectomía radical en 27 (49,1%). El volumen prostático (Vp) ≤ 60cc y el número de cilindros positivos >1 en la biopsia diagnóstica (p = 0,05) se asociaron con mayor tasa de reclasificación en el análisis univariante (p < 0,05). En el análisis multivariante, estas dos variables se correlacionaron significativamente con una mayor tasa de reclasificación (Vp ≤ 60 cc: OR 4,39, p = 0,04; >1 cilindro positivo en la biopsia diagnóstica: OR 2,48, p = 0,03). Conclusiones Se ha objetivado que el volumen ecográfico inicial y el número de cilindros positivos en la biopsia diagnóstica son factores de riesgo independientes para la reclasificación. El antígeno prostático específico (PSA) inicial, la lateralidad de los cilindros afectos y la densidad de PSA no fueron elementos predictores de progresión en nuestra serie (AU)

Introduction and Objective Active surveillance (AS) has been established as a therapeutic strategy in patients with low-risk prostate cancer. Demographic and anatomopathological factors that increase the probability of reclassifying patients have been identified. Materials and Methods Laboratory and histopathological data were collected from 116 patients included on AS since 2014. Univariate analysis was performed with Chi-square, t-student and Kendall's Tau, multivariate analysis according to logistic regression and Kaplan-Meier curves were calculated. Results Of the 116 patients in AS, the median age at diagnosis was 66 years and the median follow-up was 13 months (2-72). Of these, 61 (52.6%) are still on surveillance, while 55 (47.4%) have left the program, mostly due to histological progression (52 patients (45.2%)); radical prostatectomy was performed in 27 (49.1%). Prostate volume (PV) ≤ 60cc and the number of positive cylinders > 1 in diagnostic biopsy (p = 0.05) were associated with higher reclassification rate in univariate analysis (p < 0.05). Multivariate analysis showed that these two variables significantly correlated with higher reclassification rate (PV 60 cc: OR 4.39, p = 0.04; > 1 positive cylinder at diagnostic biopsy: OR 2.48, p = 0.03). Conclusions It has been shown that initial ultrasound volume and the number of positive cylinders in the diagnostic biopsy are independent risk factors for reclassification. Initial PSA, laterality of the affected cylinders and PSA density were not predictive factors of progression in our series (AU)

Desarrollo e implementación de una unidad de inmunoterapia en un servicio de urología / Development and implementation of an immunotherapy unit in a urology department

Introducción La inmunoterapia está revolucionando el tratamiento del cáncer, siendo los anticuerpos monoclonales dirigidos contra moléculas reguladoras del punto de control la terapia más ampliamente utilizada en la actualidad. Un total de seis fármacos inhibidores del punto de control inmunitario (CPI) han sido aprobados por la U.S. Food and Drug Administration (FDA) y por la European Medicines Agency (EMA) para su uso en diversos tumores sólidos del aparato genitourinario. Material y métodos Se revisó la literatura y se analizó la metodología y experiencia propia adquirida para instaurar el tratamiento con CPI en un servicio de Urología. Resultados Se describen los requisitos recomendables desde el punto de vista formativo, logístico y procedimental para implementar una unidad de inmunoterapia en un servicio de Urología que permita ofrecer con seguridad el tratamiento experto con CPI a los pacientes con tumores genitourinarios. Conclusiones El cumplimiento del programa propuesto garantiza la administración segura de CPI en un entorno hospitalario (AU)

Introduction Immunotherapy is revolutionizing cancer treatment, with monoclonal antibodies directed against checkpoint regulatory molecules currently being the most widely used therapy. A total of six immune checkpoint inhibitor (CPI) drugs have been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in various solid tumors of the genitourinary tract. Material and methods the literature is reviewed and the methodology, as well as our own experience, are analyzed to establish treatment with CPI in a urology department. Results The requirements recommended in terms of training, logistics and procedure are described in order to safely offer expert treatment with CPI to patients with genitourinary tumors. Conclusions Compliance with the proposed program ensures safe administration of immune checkpoint inhibitors in a hospital setting (AU)

Development and implementation of an immunotherapy unit in a urology department.

INTRODUCTION: Immunotherapy is revolutionizing cancer treatment, with monoclonal antibodies directed against checkpoint regulatory molecules currently being the most widely used therapy. A total of six immune checkpoint inhibitor (CPI) drugs have been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in various solid tumors of the genitourinary tract. MATERIAL AND METHODS: The literature is reviewed and the methodology, as well as our own experience, are analyzed to establish treatment with CPIs in a urology department. RESULTS: The requirements recommended in terms of training, logistics and procedure are described in order to safely offer expert treatment with CPIs to patients with genitourinary tumors. CONCLUSIONS: Compliance with the proposed program ensures safe administration of immune checkpoint inhibitors in a hospital setting.

Efecto apoptótico como biomarcador de enfermedad, severidad y seguimiento en la cistitis intersticial / Apoptotic effect as biomarker of disease, severity and follow-up in interstitial cystitis

Objetivo: Estudiar si el test de efecto apoptótico podría servir como biomarcador de severidad en el síndrome de dolor vesical/cistitis intersticial. Material y métodos: Se realizó un estudio prospectivo entre enero de 2010 y enero de 2015, se incluyeron 57 pacientes diagnosticadas de cistitis intersticial y 49 de dolor pélvico crónico de origen ginecológico. Se expuso la orina a cultivos celulares y se analizó su capacidad para inducir apoptosis en ellos. Posteriormente se llevó acabó un análisis estadístico para valorar si el efecto apoptótico se asociaba con la sintomatología. Resultados: Al realizar un análisis de la asociación entre el grado del efecto apoptótico y la sintomatología de las pacientes con cistitis intersticial, se observó un aumento significativo de los porcentajes medios de apoptosis a medida que aumenta el grado de severidad sintomatológica. Al analizar la asociación entre el efecto apoptótico y la sintomatología, se obtuvo una correlación positiva en los pacientes con cistitis intersticial y una ausencia de correlación en los pacientes con dolor pélvico crónico de origen ginecológico. Los porcentajes de apoptosis aumentan de manera progresiva en las pacientes con cistitis intersticial a medida que presentan mayor sintomatología mientras que los pacientes con dolor pélvico crónico de origen ginecológico permanecen estables. Conclusiones: El efecto apoptótico de la orina de pacientes con cistitis intersticial podría ser un marcador de enfermedad, permitiendo diferenciar las pacientes afectas de cistitis intersticial de pacientes con dolor pélvico crónico y además poder tener una medida objetiva del grado de severidad de los síntomas

Objective: To determine whether the apoptotic effect test could serve as a biomarker of severity in bladder pain syndrome/interstitial cystitis. Material and methods: A prospective study was conducted between January 2010 and January 2015, which included 57 patients diagnosed with interstitial cystitis and 49 diagnosed with chronic pelvic pain of gynaecological origin. The urine was exposed to cell cultures, and the urine's capacity for inducing apoptosis in the cultures was analysed. A statistical analysis was then conducted to assess whether the apoptotic effect was associated with the symptoms. Results: After performing an analysis of the association between the degree of apoptotic effect and the symptoms of patients with interstitial cystitis, we observed a significant increase in the mean percentages of apoptosis as the degree of symptom severity increased. After analysing the association between the apoptotic effect and symptoms, we obtained a positive correlation in the patients with interstitial cystitis and a lack of correlation in the patients with chronic pelvic pain of gynaecological origin. The rates of apoptosis increased progressively in the patients with interstitial cystitis as the symptoms increased, while the patients with chronic pelvic pain of gynaecological origin remained stable. Conclusions: The apoptotic effect of the urine of patients with interstitial cystitis could be a marker of disease, thus differentiating patients with interstitial cystitis from patients with chronic pelvic pain. The effect could also provide an objective measure of symptom severity

Apoptotic effect as biomarker of disease, severity and follow-up in interstitial cystitis. / Efecto apoptótico como biomarcador de enfermedad, severidad y seguimiento en la cistitis intersticial.

OBJECTIVE: To determine whether the apoptotic effect test could serve as a biomarker of severity in bladder pain syndrome/interstitial cystitis. MATERIAL AND METHODS: A prospective study was conducted between January 2010 and January 2015, which included 57 patients diagnosed with interstitial cystitis and 49 diagnosed with chronic pelvic pain of gynaecological origin. The urine was exposed to cell cultures, and the urine's capacity for inducing apoptosis in the cultures was analysed. A statistical analysis was then conducted to assess whether the apoptotic effect was associated with the symptoms. RESULTS: After performing an analysis of the association between the degree of apoptotic effect and the symptoms of patients with interstitial cystitis, we observed a significant increase in the mean percentages of apoptosis as the degree of symptom severity increased. After analysing the association between the apoptotic effect and symptoms, we obtained a positive correlation in the patients with interstitial cystitis and a lack of correlation in the patients with chronic pelvic pain of gynaecological origin. The rates of apoptosis increased progressively in the patients with interstitial cystitis as the symptoms increased, while the patients with chronic pelvic pain of gynaecological origin remained stable. CONCLUSIONS: The apoptotic effect of the urine of patients with interstitial cystitis could be a marker of disease, thus differentiating patients with interstitial cystitis from patients with chronic pelvic pain. The effect could also provide an objective measure of symptom severity.

Estudio del efecto apoptótico de la orina de pacientes con cistitis intersticial como biomarcador diagnóstico / Study of the apoptotic effect of urine as a diagnostic biomarker in patients with interstitial cystitis

Introducción: El principal objetivo es valorar el efecto apoptótico de la orina de pacientes con cistitis intersticial (CI) en cultivos celulares y estudiar su valor como biomarcador diagnóstico para la CI. Material y métodos: Estudio prospectivo entre enero de 2010 y enero de 2015, en el que se incluyeron 57 pacientes diagnosticadas de CI y 50 pacientes sanas del Hospital Clínic de Barcelona y del Hospital Universitario la Fe. Se expuso la orina de dichas pacientes a cultivos celulares y se analizó su capacidad para inducir apoptosis en ellos y posteriormente, mediante citometría de flujo, se midió el grado de apoptosis, cuantificado por el porcentaje de células del ciclo celular en fase sub G0. Resultados: Los cultivos celulares expuestos a orina de pacientes con CI presentan un pico sub G1 y una fase G2, significativamente mayor que el grupo control, y en la fase S presentan un porcentaje significativamente menor al grupo control. Los valores medios de apoptosis en los cultivos de orina de pacientes con CI son significativamente muy superiores a los del grupo control. Para un valor > 10% de la prueba de apoptosis como resultado positivo, se observa una especificidad (96%) y un valor predictivo positivo (92%). Conclusiones: La orina de pacientes con CI ejerce un efecto apoptótico sobre cultivos celulares tumorales significativamente superior al que ejercen orinas de pacientes controles sanos. Un punto de corte ≥ 10% para la prueba de apoptosis presenta una sensibilidad muy baja (40%), pero tiene una especificidad muy alta (96%) pudiendo confirmar el diagnóstico de CI cuando es positiva

Introduction: The main objective of the study was to assess the apoptotic effect of urine from patients with interstitial cystitis (IC) in cell cultures and to study its value as a diagnostic biomarker for IC. Material and methods: A prospective study was conducted between January 2010 and January 2015 and included 57 patients diagnosed with IC and 50 healthy patients from the Hospital Clinic of Barcelona and the La Paz University Hospital. The urine of these patients was exposed to cell cultures, and its ability to induce apoptosis in the cultures was analysed. Using flow cytometry, we then measured the degree of apoptosis, quantified by the percentage of cells of the cell cycle in phase sub G0. Results: The cell cultures exposed to the urine of patients with IC had a sub G1 peak and a G2 phase, which was significantly greater than that of the control group, and a significantly lower percentage in the S phase than the control group. The mean apoptosis values in the urine cultures from patients with IC were significantly higher than those of the control group. Using a value > 10% of the apoptosis test as a positive result, we observed a specificity of 96% and a positive predictive value of 92%. Conclusions: The urine of patients with IC exerts an apoptotic effect on tumour cell cultures that is significantly greater than that exerted by the urine of healthy control patients. A ≥ 10% cutoff for the apoptosis test presented very low sensitivity (40%) but had a very high specificity (96%), thereby able to confirm the diagnosis of IC when positive

Study of the apoptotic effect of urine as a diagnostic biomarker in patients with interstitial cystitis. / Estudio del efecto apoptótico de la orina de pacientes con cistitis intersticial como biomarcador diagnóstico.

INTRODUCTION: The main objective of the study was to assess the apoptotic effect of urine from patients with interstitial cystitis (IC) in cell cultures and to study its value as a diagnostic biomarker for IC. MATERIAL AND METHODS: A prospective study was conducted between January 2010 and January 2015 and included 57 patients diagnosed with IC and 50 healthy patients from the Hospital Clinic of Barcelona and the La Paz University Hospital. The urine of these patients was exposed to cell cultures, and its ability to induce apoptosis in the cultures was analysed. Using flow cytometry, we then measured the degree of apoptosis, quantified by the percentage of cells of the cell cycle in phase sub G0. RESULTS: The cell cultures exposed to the urine of patients with IC had a sub G1 peak and a G2 phase, which was significantly greater than that of the control group, and a significantly lower percentage in the S phase than the control group. The mean apoptosis values in the urine cultures from patients with IC were significantly higher than those of the control group. Using a value >10% of the apoptosis test as a positive result, we observed a specificity of 96% and a positive predictive value of 92%. CONCLUSIONS: The urine of patients with IC exerts an apoptotic effect on tumour cell cultures that is significantly greater than that exerted by the urine of healthy control patients. A≥10% cutoff for the apoptosis test presented very low sensitivity (40%) but had a very high specificity (96%), thereby able to confirm the diagnosis of IC when positive.